Electron-Deficient Alloxazinium Salts: Efficient Organocatalysts of Mild and Chemoselective Sulfoxidations with Hydrogen Peroxide

A series of substituted alloxazinium perchlorates has been prepared and tested as catalysts for the oxidation of sulfides to sulfoxides with hydrogen peroxide. The logarithms of the observed rate constants of thioanisole oxidation correlate with the Hammett sigma constants of the substituents on the alloxazinium catalysts, as well as with their reduction potentials E-0 and their pK(R+) values, representing the alloxazinium salt/pseudobase equilibrium. The stronger the electron-withdrawing substituent, the more efficient is the alloxazinium catalyst. The alloxazinium salts with a cyano or trifluoromethyl group in position 8 proved to be the most efficient, operating at room temperature at small loadings, down to 0.1mol%, achieving turnover number values of up to 640 and acceleration by a factor of 350 relative to the non-catalyzed oxidation. The 8-cyanoalloxazinium perchlorate was evaluated as the best catalyst; however, due to its relatively good accessibility, the 8-(trifluoromethyl)alloxazinium perchlorate seems to be the catalyst of choice for sulfoxidations with hydrogen peroxide. It was successfully tested for the sulfoxidation of a series of aliphatic and aromatic sulfides on a preparative scale. It produced the corresponding sulfoxides in quantitative conversions and with high isolated yields (87-98%). No over-oxidation to sulfone was ever observed.